pH- and thermosensitive thin lipid layer coated mesoporous magnetic nanoassemblies as a dual drug delivery system towards thermochemotherapy of cancer.

Abstract: A new pH-sensitive and thermosensitive dual drug delivery system consisting of thin lipid layer encapsulated mesoporous magnetite nanoassemblies (MMNA) has been developed which can deliver two anticancer drugs simultaneously. The formulation of lipid layer used is 5:2:2:2w/w, DPPC:cholesterol:DSPE-PEG₂₀₀₀:MMNA. The structure, morphology and magnetic properties of MMNA and lipid coated MMNA (LMMNA) were thoroughly characterized. This hybrid system was investigated for its ability to carry two anticancer drugs as well as its ability to provide heat under an alternating current magnetic field (ACMF). A very high loading efficiency of up to ∼81% of doxorubicin hydrochloride (DOX) with an ∼0.02mgmg⁻¹ loading capacity and ∼60% of paclitaxel (TXL) with an ∼0.03mgmg⁻¹ loading capacity are obtained with LMMNA. A sustained release of drug is observed over a period of 172h, with better release, of ∼88:53% (DOX:TXL), at pH 4.3 compared to the ∼28:26% (DOX:TXL) in physiological conditions (pH 7.4). An enhanced release of ∼72 and ∼68% is recorded for DOX and TXL, respectively, during the first hour with the application of an ACMF (∼43°C). A greater in vitro cytotoxic effect is observed with the two drugs compared to them individually in HeLa, MCF-7 and HepG2 cancer cells. With the application of an ACMF for 10min, the cell killing efficiency is improved substantially due to simultaneous thermo- and chemotherapy. Confocal microscopy confirms the internalization of drug loaded MMNA and LMMNA by cells and their morphological changes during thermochemotherapy. [Copyright &y& Elsevier]